Genital infections with human papillomavirus (HPV) peak soon after young women become sexually active. Most HPV infections in young women become undetectable within a few months in standard PCR assays, suggesting that infections "clear" in the majority of cases. However, proof of actual viral clearance is lacking. If HPV persists at low levels rather than clears, it could potentially reactivate and become detectable later in life, and thus contribute to clinical illness. Low level persistence could explain the second peak in HPV detection and the increase in HPV-related disease in older women. Because HPV is the causative agent of cervical cancer, it is critically important to understand whether HPV actually clears in young women, or if HPV remains present at levels undetectable using current methods. We will therefore characterize patterns of type specific HPV infection, apparent clearance, and virus reactivation (vs. re-infection) among adolescent women. To accomplish these goals, we will use type-specific, nested PCR assays of high sensitivity to potentially identify HPV persistence during periods of apparent clearance of infection as defined by standard PCR. We will also determine the duration of HPV persistence defined by nested PCR compared to standard PCR. We will also determine if apparently cleared infection of a specific HPV type that becomes detected later is due to reactivation or re-infection. We will also perform experiments to determine if low-level persistence is associated with HPV integration, a key event in carcinogenesis of HPV. Lastly, we will develop survival models to explore factors associated with HPV persistence to determine if longer periods of HPV detection will be associated with specific sexual behaviors. PUBLIC HEALTH RELEVANCE: Human papillomavirus (HPV) infection is the cause of cervical cancer. Our study is designed to determine if HPV infections can persist in some women, or if most infections actually clear in most women. This information is important in determining why some, but not all women with HPV infection develop cancer.